The blood-brain barrier (BBB) and the blood cerebrospinal fluid barrier (BCSFB) exist to protect the brain, stringently regulating substances into and out of the brain. This report examines the ways in which these natural barriers may be overcome or circumvented to ensure that drugs can reach their intended target in the brain.Identify the five main strategies for maximizing the delivery of drugs to the brain.Understand the scientific basis of the most promising and recent technology advances.Identify the companies that are at the cutting edge of each type of delivery technology.Gain insight from quotes and opinions from leaders in the field of CNS drug delivery.Assess which types of delivery technology are best suited to which types of drug and therapy area.Increasingly, drug delivery specialists are harnessing endogenous BBB mechanisms such as receptormediated delivery pathways with nano-enabled platform technologies to improve the uptake and targeted delivery of substances into the brain.Improvements in intranasal delivery devices and advances in formulation technologies have enabled researchers to deliver a wide range of substances in therapeutic doses into the olfactory regions. Medical device companies Kurve Technology, Impel NeuroPharma, and OptiNose have all developed devices that are compatible with intranasal delivery.Chemical modification (e.g. lipidation and cationization) can be used to improve passive delivery across the blood-brain barrier but is rarely used in isolation. Permeability enhancers can be used to transiently disrupt the BBB to allow the passage of drugs into the CNS, but they have yet to be fully validated in the clinic.Which delivery technologies can be considered for a drug that needs to achieve high CNS penetration?What types of chemical modification have been applied and how successful have these been?What role can nanotechnology play in drug delivery?How well validated are the delivery technologies and which have data from human trials?Are there in indications in which the problems of blood-brain barrier penetration can be justifiably circumvented by direct injection or implantation?

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EXECUTIVE SUMMARY

•Strategies for drug delivery to the brain

Introduction

•Key factors in the development of improved methods of drug delivery to the central nevous system

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